ArticleThe Journal of biological chemistry2018
PTAP motif duplication in the p6 Gag protein confers a replication advantage on HIV-1 subtype C.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Enhanced strand transfer and mismatch extension by HIV-1C reverse transcriptase promote sequence motif duplication.Journal of virology · 2026Article
- Evasion of CARD8 activation during HIV-1 assembly.Science advances · 2025Article
- Article
- Proximity Ligation Assay to Detect the Proximity Between Host Proteins and Viral Proteins of HIV-1.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Enhanced Transcriptional Strength of HIV-1 Subtype C Minimizes Gene Expression Noise and Confers Stability to the Viral Latent State.Journal of virology · 2023Article
- Enhanced Transmissibility and Decreased Virulence of HIV-1 CRF07_BC May Explain Its Rapid Expansion in China.Microbiology spectrum · 2022Article
- Tsg101/ESCRT-I recruitment regulated by the dual binding modes of K63-linked diubiquitin.Structure (London, England : 1993) · 2022Article
- Review
- Review
- The Evolution of Regulatory Elements in the Emerging Promoter-Variant Strains of HIV-1 Subtype C.Frontiers in microbiology · 2021Article
- Genetic Analysis of the Full-LengthViruses · 2019Article
- Article
- HIV-1 Subtype C with PYxE Insertion Has Enhanced Binding of Gag-p6 to Host Cell Protein ALIX and Increased Replication Fitness.Journal of virology · 2019Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV-1 subtype C (HIV-1C) may duplicate longer amino acid stretches in the p6 Gag protein, leading to the creation of an additional Pro-Thr/Ser-Ala-Pro (PTAP) motif necessary for viral packaging. However, the biological significance of a duplication of the PTAP motif for HIV-1 replication and pathogenesis has not been experimentally validated. In a longitudinal study of two different clinical cohorts of select HIV-1 seropositive, drug-naive individuals from India, we found that 8 of 50 of these individuals harbored a mixed infection of viral strains discordant for the PTAP duplication. Conventional and next-generation sequencing of six primary viral quasispecies at multiple time points disclosed that in a mixed infection, the viral strains containing the PTAP duplication dominated the infection. The dominance of the double-PTAP viral strains over a genetically similar single-PTAP viral clone was confirmed in viral proliferation and pairwise competition assays. Of note, in the proximity ligation assay, double-PTAP Gag proteins exhibited a significantly enhanced interaction with the host protein tumor susceptibility gene 101 (Tsg101). Moreover, Tsg101 overexpression resulted in a biphasic effect on HIV-1C proliferation, an enhanced effect at low concentration and an inhibitory effect only at higher concentrations, unlike a uniformly inhibitory effect on subtype B strains. In summary, our results indicate that the duplication of the PTAP motif in the p6 Gag protein enhances the replication fitness of HIV-1C by engaging the Tsg101 host protein with a higher affinity. Our results have implications for HIV-1 pathogenesis, especially of HIV-1C.
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